The focus of this project is to delineate JC virus (JCV) genotypes circulating in humans, with reference to people of African origin, including African-Americans. In addition,the neuropathology of progressive multifocal leukoencephalopathy(PML) in AIDS patients and others will be studied with a view to ascertain the possible biological effects of African genotypes of JCV and other genotype specific differences in the clinical presentation and natural history of PML. WORK IN PROGRESS: (1) 204 urine samples have been collected from African Americans from the Southeastern United States, analyzed by PCR and DNA sequence studies to delineate the genotype profile of JCV excreted in the urine of this group when compared to other ethnic groups in the United States (manuscript in preparation). Sample collection was facilitated by collaboration with the Department of Pathology, Howard University Hospital, Washington D.C. (2) 115 urine samples have been collected from children and adolescents from a US urban population to determine the JCV genotypes circulating in this age group. Samples have been sequenced, pending systematic analysis. (3) 300 plus urine samples have been collected from West African tribes from Nigeria and Ivory Coast and are presently being analyzed for JCV genotypes. This will allow further comparisons with JCV genotypes in African Americans and other ethnic minorities in the USA. (4) 68 urine samples were collected from the Biaka Pygmies and Bantu of Central Africa. JCV genotypes have been sequenced and published(see reference below). BK virus genotypes are undergoing analysis for possible publication. (5)A retrospective study of approximately 100 cases of PML from 1970-1997 archival material at Armed Forces Institute of Pathology (AFIP), Washington D.C. is being conducted in collaboration with the Department of Neuropathology at AFIP. (6) A genotype profile of JCV genotypes in a Brazilian urban population is planned in conjunction with the Department of Microbiology, University of Rio de Janeiro, Brazil. Sample collection is in progress.